Picroside II attenuates hyperhomocysteinemia‐induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis
Open accessAbstract
Picroside II (P‐II), one of the main active components of scrophularia extract, which have anti‐oxidative, anti‐inflammatory effects, but its effect on hyperhomocysteinemia (HH cy) induced endothelial injury remains to be determined. Here, we test whether P‐II protects HH cy‐induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVEC s, and in hyperhomocysteinemia mouse models, we found that HH cy decreased endothelial SIRT 1 expression and increased LOX‐1 expression, subsequently causing reactive oxygen species generation, up‐regulation of NADPH oxidase activity and NF‐κB activation, thereby promoting pro‐inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or si RNASIRT 1 increased LOX‐1 expression, whereas overexpression of SIRT 1 decreased LOX‐1 expression markedly. P‐II treatment significantly increased SIRT 1 expression and reduced LOX‐1 expression, and protected against endothelial cells from Hcy‐induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT 1 or overexpression of LOX‐1 attenuated the therapeutic effects of P‐II. In conclusion, our results suggest that P‐II prevents the Hcy induced endothelial damage probably through regulating the SIRT 1/LOX‐1 signaling pathway.
AI snapshot
Written from the paper’s full text.
TL;DR
Picroside II (P‐II) reduced hyperhomocysteinemia (HHcy)‐induced endothelial oxidative stress, inflammation, and apoptosis in HUVECs and C57BL mice, apparently by increasing SIRT1 and decreasing LOX‐1. Blocking SIRT1 or overexpressing LOX‐1 attenuated P‐II’s protective effects.
Key findings
- In HHcy mice, P‐II treatment (10 mg/kg or 60 mg/kg orally for 8 weeks after 12 weeks of methionine‐rich diet) reduced plasma Hcy, decreased aortic NADPH oxidase activity and plasma MDA, and increased plasma SOD activity; EX527 partly abolished these effects.
- HHcy increased LOX‐1 and decreased SIRT1 expression in mouse aorta and HUVECs; P‐II increased SIRT1 and decreased LOX‐1, while SIRT1 blockade with Ex527 or siRNA increased LOX‐1 and attenuated P‐II protection.
- In HUVECs exposed to 100 μmol Hcy for 24 hours, P‐II (50, 100, 200 μg/mL) reduced ROS, MDA, NADPH oxidase activity, NF‐κB p65 activation, IL‐6/IL-8/TNF-α production, caspase-3 activity, and Annexin V‐detected apoptosis, and restored SOD and CAT activity.
- Overexpression of LOX‐1 partly abolished P‐II‐induced protection against HHcy‐induced NADPH oxidase activation, proinflammatory cytokine production, and apoptosis.
Methods
- In vivo: 50 C57BL mice randomized into five groups (10 each): sham control, HHcy, HHcy+P‐II low dose (10 mg/kg), HHcy+P‐II high dose (60 mg/kg), and HHcy+P‐II high dose+EX527 (1.2 mM EX527, 5 μL intravenously 2 hours before P‐II). HHcy was induced by L‐methionine‐rich diet for 12 weeks, then P‐II or PBS was given orally for another 8 weeks.
- In vitro: HUVECs were incubated with 100 μmol Hcy for 24 hours, with or without P‐II preincubation (50, 100, 200 μg/mL for 24 hours), siRNA LOX‐1, SIRT1 siRNA, LOX‐1 cDNA, or SIRT1 cDNA.
- Main analyses: RT‐PCR, Western blotting, ELISA for IL‐6/IL‐8/CXCL15/TNF‐α, ROS and NADPH oxidase assays, MDA/SOD/CAT measurements, CCK‐8 viability, Annexin V‐FITC/PI flow cytometry, and caspase‐3 activity; statistics used t tests, one‐way/two‐way ANOVA, Bonferroni post hoc, with P < 0.05 significant.
Limitations
- The paper states no limitations section.
- Evident from the text: the study is limited to HUVECs and a mouse HHcy model, with no human clinical outcomes; mechanistic causality relies on in vitro overexpression/knockdown and an in vivo SIRT1 inhibitor, and the authors often use speculative language (“probably,” “speculated”).
- Evident from the text: figure legends contain inconsistencies in methionine concentration/group descriptions (e.g., 1% vs 2% methionine), and toxicity assessment is limited to HUVEC viability/apoptosis with P‐II.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
10 of 20 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Hyperhomocysteinemia up-regulates LOX-1 expression in human mononuclear and endothelial cells.
“Much studies have shown that HHcy up‐regulated human mononuclear and endothelial cells LOX‐1 expression,7, 8”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [7] Holven KB, Scholz H, Halvorsen B, Aukrust P, Ose L, Nenseter MS. Hyperhomocysteinemic subjects have enhanced expression of lectin‐like oxidized LDL receptor‐1 in mononuclear cells. J Nutr. 2003; 133: 3588‐ 3591. 14608078 source
The Results (‘Levels of LOX-1 mRNA in PBMC’) report higher LOX-1 mRNA in mononuclear cells from hyperhomocysteinemic subjects than in healthy controls. The discussion (under ‘FIGURE 1’) mentions enhanced LOX-1 expression in cultured bovine aortic endothelial cells, not human endothelial cells; that part of the claim is unsupported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [8] Hung CH, Chan SH, Chu PM, Tsai KL. Homocysteine facilitates LOX‐1 activation and endothelial death through the PKCbeta and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia. Clin Sci (Lond). 2015; 129: 477‐ 487. 25982096 source
- Premisecitation
SIRT1 activation is an effective approach to manage hyperhomocysteinemia-induced oxidative stress.
“Previous reports have suggested that SIRT1 activation is an effective approach to manage HHcy‐induced oxidative stress,33, 34”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [33] Ma CH, Chiua YC, Wu CH, et al. Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1/AMPK pathway: a possible link between hyperhomocysteinemia and osteoarthritis. Redox Biol. 2018; 15: 504‐ 512. 29413962 PMC5881416 source
The Results section, “Homocysteine-induced oxidative stress is reversed by activation of SIRT1/AMPK/PGC-1α signaling,” reports that SIRT1 overexpression reduced the oxidative-stress effects of homocysteine in human chondrocytes. This supports SIRT1 activation as a potential approach, but the cell experiments do not establish that it effectively manages hyperhomocysteinemia-induced oxidative stress in patients. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [34] Chen Y, Liu H, Wang X, Zhang H, Liu E, Su X. Homocysteine up‐regulates endothelin type A receptor in vascular smooth muscle cells through Sirt1/ERK1/2 signaling pathway. Microvasc Res. 2017; 114: 34‐ 40. 28579512 source
- Findingown data
siRNA-LOX-1 reverses hyperhomocysteinemia-induced NF-κB activation and IL-6, IL-8, and TNF-α production.
“siRNA‐LOX‐1 reversed the NF‐κB activation (Figure 9A) and IL‐6, IL‐8 and TNF‐α production induced by HHcy”
Quote in the paperSubstantial claim - Findingown data
Plasma levels of hyperhomocysteinemia-associated inflammatory cytokines were elevated in hyperhomocysteinemic mice.
“Similarly, plasma levels of HHcy‐associated inflammatory cytokines were also elevated.”
Quote in the paperSubstantial claim - Findingown data
Picroside II reduces hyperhomocysteinemia-induced NADPH oxidase activation and reactive oxygen species formation in HUVECs in a concentration-dependent manner.
“preincubation with P‐II reduced the HHcy‐induced NADPH oxidase activation and ROS formation in a concentration‐dependent manner”
Quote in the paperSubstantial claim
- Findingown data
Blockade of SIRT1 with Ex527 or siRNA SIRT1 increases LOX-1 expression.
“Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX‐1 expression”
- Also stated in: § The LOX‐1 receptor and SIRT1 participate in P‐II ‐involved cell protection · plain
“blockade of SIRT1 with siRNA SIRT1 decreased SIRT1 (Figure 10A) and increased LOX‐1(Figure 10B)”
Quote in the paperSubstantial claim - Also stated in: § The LOX‐1 receptor and SIRT1 participate in P‐II ‐involved cell protection · plain
- Findingown data
Hyperhomocysteinemia activates NF-κB in endothelial cells.
“NF‐κB activation”
- Also stated in: § Picroside II mediated the homocysteine induced endothelial inflammation in HUVECs · hedged
“HHcy induce the activation of NF‐κB, as indicated by nuclear translocation and DNA binding of its p65 subunit”
Quote in the paperSubstantial claim - Also stated in: § Picroside II mediated the homocysteine induced endothelial inflammation in HUVECs · hedged
- Findingown data
Hyperhomocysteinemia increased the expression of CXCL15, TNF-α and IL-6 in the thoracic arteries of hyperhomocysteinemic mice.
“HHcy increased the expression of CXCL15 (human IL‐8 homologous), TNF‐α and IL‐6 in the thoracic arteries of HHcy mice.”
Quote in the paperSubstantial claim - Findingown data
Picroside II treatment reversed hyperhomocysteinemia-induced changes in inflammatory cytokines.
“These changes in inflammatory cytokines were reversed after P‐II treatment”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia up-regulates NADPH oxidase activity in endothelial cells and vascular tissue.
“up‐regulation of NADPH oxidase activity”
- Also stated in: § Picroside II attenuated vascular oxidative stress and inflammation in hyperhomocysteinaemic mice · plain
“aortic endothelial NADPH oxidase activity was increased markedly in the HHcy mice group”
- Also stated in: § Picroside II Inhibits ROS formation and NADPH oxidase activation in HUVECs · plain
“HHcy significantly increased ROS and MDA levels and NAPDH oxidase activity”
Quote in the paperSubstantial claim - Also stated in: § Picroside II attenuated vascular oxidative stress and inflammation in hyperhomocysteinaemic mice · plain
- Findingown data
Picroside II down-regulates hyperhomocysteinemia-induced apoptosis in HUVECs in a concentration-dependent manner.
“When cells were incubated with P‐II, the apoptotic process was dramatically down‐regulated in a concentration‐dependent manner”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia-induced reactive oxygen species formation and cell apoptosis are abrogated by siRNA LOX-1.
“HHcy‐induced ROS formation (Figure 5A) and cell apoptosis (Figure 7A) were abrogated by pretreatment with siRNA LOX‐1.”
Quote in the paperSubstantial claim - Findingown data
Picroside II protects endothelial cells from Hcy-induced oxidative injury, inflammation and apoptosis.
“protected against endothelial cells from Hcy‐induced oxidative injury, inflammation and apoptosis”
- Also stated in: § DISCUSSION · hedged
“P‐II, the main active ingredient in the root department of Chinese medicine Picrorhiza scrophulariiflora, could reduce HHcy‐induced endothelial oxidase stress, inflammation and cell apoptosis in vitro and in vivo.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Findingown data
Picroside II, NAC, and Apocynin restore Hcy-induced suppression of SOD and CAT activity in HUVECs.
“P‐II at 50, 100 and 200 μg/mL, NAC and Apocynin significantly restored the suppression of SOD and CAT activity induced by HHcy.”
Quote in the paperSubstantial claim - Findingown data
Overexpression of SIRT1 decreases LOX-1 expression markedly.
“whereas overexpression of SIRT1 decreased LOX‐1 expression markedly”
- Also stated in: § The LOX‐1 receptor and SIRT1 participate in P‐II ‐involved cell protection · plain
“overexpressing of SIRT1 with SIRT1cDNA increased SIRT1 (Figure 10C,D) and decreased LOX‐1 (Figure 10E)”
Quote in the paperSubstantial claim - Also stated in: § The LOX‐1 receptor and SIRT1 participate in P‐II ‐involved cell protection · plain
- Findingown data
Picroside II inhibits hyperhomocysteinemia-induced NF-κB activation in a concentration-dependent manner.
“HHcy induce the activation of NF‐κB, as indicated by nuclear translocation and DNA binding of its p65 subunit, which was inhibited by P‐II in a concentration dependent manner.”
Quote in the paperSubstantial claim - Findingown data
Hcy decreases SOD and CAT activity in HUVECs.
“addition of Hcy resulted in a marked decrease in SOD and CAT activity”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia elevates caspase-3 activity and cleaved caspase-3 levels in HUVECs.
“The Caspase‐3 activity displayed a similar change after adding P‐II into the culture media of HUVECs. Western blotting showed the activity of Caspase‐3 and the cleaved Caspase‐3 levels were obviously elevated after HHcy.”
Quote in the paperSubstantial claim - Findingown data
Overexpressing LOX-1 partly abolishes Picroside II-induced protection against hyperhomocysteinemia-induced NADPH oxidase activation, pro-inflammatory cytokine production, and cell apoptosis.
“Overexpressing of LOX‐1 (LOX‐1cDNA), however, partly abolished the P‐II‐induced protection against HHcy‐ induced NADPH oxidase activation (Figure 5A‐E) as well as pro‐inflammatory cytokines production (Figure 6A‐F) and cell apoptosis (Figure 7A,B).”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia increases reactive oxygen species generation in endothelial cells.
“subsequently causing reactive oxygen species generation”
- Also stated in: § Picroside II Inhibits ROS formation and NADPH oxidase activation in HUVECs · plain
“Hcy significantly increase ROS production after treatment for 24 hours”
Quote in the paperSubstantial claim - Also stated in: § Picroside II Inhibits ROS formation and NADPH oxidase activation in HUVECs · plain
- Findingown data
Treatment with 100 and 150 μM Hcy increases LOX-1 mRNA and protein levels in human endothelial cells.
“Treatment with 100 and 150 μM Hcy, The mRNA and protein levels of LOX‐1 were dramatically increased in human endothelial cells”
Quote in the paperSubstantial claim - Findingown data
EX527 partly abolished Picroside II-induced protection against hyperhomocysteinemia-induced SIRT1 inhibition, NADPH oxidase activation, LOX-1 up-regulation, and increase of pro-inflammatory cytokine production.
“EX527 partly abolished the P‐II‐induced protection against HHcy‐induced SIRT1 inhibition (Figure 4B), NADPH oxidase activation (Figure 2A), LOX‐1 up‐regulation (Figure 4A), and the increase of pro‐inflammatory cytokines production (Figure 3A‐F).”
Quote in the paperSubstantial claim - Findingown data
Picroside II at 50, 100, and 200 μg/mL for 48 hours did not affect HUVEC viability or apoptosis.
“cell viability and cell apoptosis were not affected by treatment of HUVECs with 50 μg/mL, 100 μg/mL, 200 μg/mL of P‐II for 48 hours.”
Quote in the paperSubstantial claim - Findingown data
Picroside II reverses hyperhomocysteinemia-induced up-regulation of IL-8, IL-6, and TNF-α in HUVECs.
“pretreatment with P‐II reversed the up‐regulation of IL‐8, IL‐6 and TNF‐α induced by HHcy”
Quote in the paperSubstantial claim - Findingown data
Picroside II decreases caspase-3 activity and cleaved caspase-3 levels in HUVECs in a concentration-dependent manner.
“When the cells were pretreated with increasing concentrations of P‐II, the Caspase‐3 activity and the cleaved Caspase‐3 levels were gradually decreased”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia promotes pro-inflammatory response and cell apoptosis in endothelial cells.
“thereby promoting pro‐inflammatory response and cell apoptosis”
- Also stated in: § Picroside II attenuated vascular oxidative stress and inflammation in hyperhomocysteinaemic mice · plain
“HHcy increased the expression of CXCL15 (human IL‐8 homologous), TNF‐α and IL‐6 in the thoracic arteries of HHcy mice.”
- Also stated in: § Picroside II reduces HHcy‐induced endothelial apoptosis in HUVECs · plain
“HHcy resulted in significant increase in HUVECs apoptosis.”
Quote in the paperSubstantial claim - Also stated in: § Picroside II attenuated vascular oxidative stress and inflammation in hyperhomocysteinaemic mice · plain
- Findingown data
Hyperhomocysteinemia increases MDA levels in HUVECs.
“HHcy significantly increased ROS and MDA levels and NAPDH oxidase activity”
Quote in the paperSubstantial claim - Findingown data
Hyperhomocysteinemia increases apoptosis in HUVECs.
“HHcy resulted in significant increase in HUVECs apoptosis.”
Quote in the paperSubstantial claim - Interpretationown data
Hyperhomocysteinemia binds to LOX-1, which leads to consequent changes.
“This suggests that HHcy binds to LOX‐1 which leads to consequent changes.”
Quote in the paperSubstantial claim - Interpretationown data
Picroside II attenuates hyperhomocysteinemia-induced LOX-1 up-regulation via activation of the ubiquitination of SIRT1.
“The data from our study demonstrated that P‐II attenuated the up‐regulation of HHcy‐induced LOX‐1 via activation of the ubiquitination of SIRT1.”
Quote in the paperSubstantial claim - Interpretationown data
Picroside II restores endothelial function by normalization of reactive oxygen species and antioxidant defenses.
“These findings support a notion that P‐II restores endothelial function by normalization of ROS and antioxidant defenses (Figure 11).”
Quote in the paperSubstantial claim - Interpretationown data
Picroside II prevents Hcy-induced endothelial damage probably through regulating the SIRT1/LOX-1 signaling pathway.
“In conclusion, our results suggest that P‐II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX‐1 signaling pathway.”
- Also stated in: § DISCUSSION · hedged
“In summary, the results from our study indicated that P‐II prevented HHcy‐induced LOX‐1‐mediated HUVECs injury, probably with its anti‐oxidative and anti‐inflammatory effects.”
Quote in the paperSubstantial claim - Also stated in: § DISCUSSION · hedged
- Interpretationown data
Picroside II prevents hyperhomocysteinemia-induced LOX-1-mediated HUVEC injury, probably with anti-oxidative and anti-inflammatory effects.
“In summary, the results from our study indicated that P‐II prevented HHcy‐induced LOX‐1‐mediated HUVECs injury, probably with its anti‐oxidative and anti‐inflammatory effects.”
Quote in the paperSubstantial claim
- May combine two claims. 17
- Classified as probably not a substantial claim. 8
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationLOX-1 up-regulation by hyperhomocysteinemia prompts reactive oxygen species formation, induces pro-apoptotic signal transduction and nitric oxide catabolism, and consequently causes oxidative injury and endothelial cell death.
“which prompts reactive oxygen species (ROS) formation,8, 9 induces pro‐apoptotic signal transduction and nitric oxide (NO) catabolism, consequently causing oxidative injury and the endothelial cells death.10, 11”
Quote in the paperSubstantial claim1 of 4 sources checked- cites [8] Hung CH, Chan SH, Chu PM, Tsai KL. Homocysteine facilitates LOX‐1 activation and endothelial death through the PKCbeta and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia. Clin Sci (Lond). 2015; 129: 477‐ 487. 25982096 source
- cites [9] Chen XP, Xun KL, Wu Q, Zhang TT, Shi JS, Du GH. Oxidized low density lipoprotein receptor‐1 mediates oxidized low density lipoprotein‐induced apoptosis in human umbilical vein endothelial cells: role of reactive oxygen species. Vascul Pharmacol. 2007; 47: 1‐ 9. 17433786 source
- cites [10] Li D, Mehta JL. Antisense to LOX‐1 inhibits oxidized LDL‐mediated upregulation of monocyte chemoattractant protein‐1 and monocyte adhesion to human coronary artery endothelial cells. Circulation. 2000; 101: 2889‐ 2895. 10869259 source
The Effect of LOX-1 on HCAEC Injury section (page unavailable) reports that blocking LOX-1 prevented oxidized-LDL-mediated endothelial cell injury. The discussion also reports MAPK activation and cites apoptosis and inhibition of cNOS activity. The paper does not establish the claimed hyperhomocysteinemia-driven pathway, ROS formation, or nitric oxide catabolism. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [11] Lu J, Yang JH, Burns AR, et al. Mediation of electronegative low‐density lipoprotein signaling by LOX‐1: a possible mechanism of endothelial apoptosis. Circ Res. 2009; 104: 619‐ 627. 19150883 source
May combine two claims.
PremisecitationLOX-1 is an essential receptor for oxidized low-density lipoprotein and plays a vital role in the atherosclerotic process.
“Lectin‐like oxLDL receptor‐1 (LOX‐1) is an essential receptor for oxide low‐density lipoprotein (oxLDL),5 and plays a vital role in atherosclerotic process.6”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [5] Sugimoto K, Ishibashi T, Sawamura T, et al. LOX‐1‐MT1‐MMP axis is crucial for RhoA and Rac1 activation induced by oxidized low‐density lipoprotein in endothelial cells. Cardiovasc Res. 2009; 84: 127‐ 136. 19487339 source
The Introduction says endothelial dysfunction is crucial to the initiation and development of atherosclerosis and that the ox-LDL–LOX-1 axis appears crucial to endothelial dysfunction in coronary artery disease. This supports a role for LOX-1, but the paper does not establish the broader, unqualified claim that LOX-1 plays a vital role in the atherosclerotic process. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [6] Hofmann A, Brunssen C, Morawietz H. Contribution of lectin‐like oxidized low‐density lipoprotein receptor‐1 and LOX‐1 modulating compounds to vascular diseases. Vascul Pharmacol. 2017; 17: 30171‐ 30174. 29056472 source
May combine two claims.
PremisecitationHyperhomocysteinemia can induce vascular endothelial injury and is one of the main risk factors for cardiovascular diseases.
“Hyperhomocysteinemia (HHcy) can induces vascular endothelial injury, and has been determined to be one of the main risk factors for cardiovascular diseases,2, 3”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [2] Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta‐analysis. JAMA. 2002; 288: 2015‐ 2022. 12387654 source
The Comment section reports a modest association between homocysteine levels and ischemic heart disease and stroke risk, but says causality remains uncertain. The paper does not establish homocysteine as a main cardiovascular risk factor or show that it induces vascular endothelial injury (searched for endothelial injury and related mechanisms). (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [3] Hofmann MA, Lalla E, Lu Y, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest. 2001; 107: 675‐ 683. 11254667 PMC208940 source
The Introduction reports that elevated homocysteine is associated with increased cardiovascular risk and may cause oxidative damage at the vascular interface; it also describes impaired endothelial-dependent vasodilation in people with experimentally induced hyperhomocysteinemia. This supports the endothelial-injury point, but the paper does not establish that hyperhomocysteinemia is *one of the main* cardiovascular risk factors. (LLM, conf=0.85)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationPicroside II has anti-oxidative and anti-inflammatory effects.
“Picroside II (P‐II), one of the main active components of scrophularia extract, has shown its anti‐oxidative, anti‐inflammatory effects.14, 15, 16”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [14] Wang T, Zhai L, Zhang H, Zhao L, Guo Y. Picroside II Inhibits the MEK‐ERK1/2‐COX2 Signal Pathway to Prevent Cerebral Ischemic Injury in Rats. J Mol Neurosci. 2015; 57: 335‐ 351. 26240040 source
- cites [15] Wang L, Liu XH, Chen H, et al. Picroside II protects rat kidney against ischemia/reperfusion‐induced oxidative stress and inflammation by the TLR4/NF‐kappaB pathway. Exp Ther Med. 2015; 9: 1253‐ 1258. 25780418 PMC4353747 source
- cites [16] Li JZ, Yu SY, Mo D, Tang XN, Shao QR. Picroside inhibits hypoxia/reoxygenation‐induced cardiomyocyte apoptosis by ameliorating mitochondrial function through a mechanism involving a decrease in reactive oxygen species production. Int J Mol Med. 2015; 35: 446‐ 452. 25421707 source
Classified as probably not a substantial claim.
PremisecitationSIRT1 protects the cardiovascular system from degeneration and oxidative injuries.
“SIRT1, an important anti‐atherosclerosis molecule, protects the cardiovascular system from degeneration and oxidative injuries.31, 32”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [31] Zarzuelo MJ, Lopez‐Sepulveda R, Sanchez M, et al. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem Pharmacol. 2013; 85: 1288‐ 1296. 23422569 source
- cites [32] Kitada M, Kume S, Imaizumi N, Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn‐SOD dysfunction in AMPK/SIRT1‐independent pathway. Diabetes. 2011; 60: 634‐ 643. 21270273 PMC3028365 source
The Results section reports that resveratrol reduced oxidative stress in renal cells even when SIRT1 was knocked down; the Discussion likewise describes a SIRT1-independent effect in diabetic kidneys. Searches for cardiovascular protection, vascular degeneration, and anti-atherosclerotic effects found no passage in our copy attributing those effects to SIRT1. Page numbers were unavailable. (LLM, conf=0.76)
Experimental — accuracy not yet measured
May combine two claims.
PremisecitationSIRT1 decreases LOX-1 expression and NF-κB activation.
“and SIRT1 decreased the LOX‐1 expression level and NF‐κB activation.8, 25”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [8] Hung CH, Chan SH, Chu PM, Tsai KL. Homocysteine facilitates LOX‐1 activation and endothelial death through the PKCbeta and SIRT1/HSF1 mechanism: relevance to human hyperhomocysteinaemia. Clin Sci (Lond). 2015; 129: 477‐ 487. 25982096 source
- cites [25] Chan SH, Hung CH, Shih JY, et al. Exercise intervention attenuates hyperhomocysteinemia‐induced aortic endothelial oxidative injury by regulating SIRT1 through mitigating NADPH oxidase/LOX‐1 signaling. Redox Biol. 2018; 14: 116‐ 125. 28888894 PMC5596261 source
May combine two claims.
Findingown dataOverexpressing SIRT1 reverses hyperhomocysteinemia-induced NF-κB activation, reactive oxygen species formation, IL-6, IL-8, and TNF-α production, and cell apoptosis.
“overexpressing of SIRT1 reversed NF‐κB activation (Figure 9A), ROS formation (Figure 5A‐C), IL‐6, IL‐8, TNF‐α production (Figure 6A‐F) and cell apoptosis induced by HHcy (Figure 9B‐D).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAortic endothelial NADPH oxidase activity was increased in hyperhomocysteinemic mice and decreased after Picroside II treatment.
“aortic endothelial NADPH oxidase activity was increased markedly in the HHcy mice group, however after treatment with P‐II, it was decreased”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHyperhomocysteinemia decreases endothelial SIRT1 expression and increases LOX-1 expression in vivo and in vitro.
“we found that HHcy decreased endothelial SIRT1 expression and increased LOX‐1 expression”
- Also stated in: § Expression of LOX‐1, SIRT1 in control and hyperhomocysteinaemic mice · plain
“Compared with control animals, the LOX‐1 protein expression increased and SIRT1 expression decreased markedly in the HHcy group”
- Also stated in: § DISCUSSION · plain
“Hcy decreased SIRT1 expression significantly”
Quote in the paperSubstantial claim- Also stated in: § Expression of LOX‐1, SIRT1 in control and hyperhomocysteinaemic mice · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown datasiRNA SIRT1 decreases SIRT1 expression.
“blockade of SIRT1 with siRNA SIRT1 decreased SIRT1 (Figure 10A)”
Quote in the paperNot a substantial claimMay combine two claims. The quote only partly states this claim.
Findingown dataPicroside II treatment increases SIRT1 expression and reduces LOX-1 expression, with LOX-1 reduction being concentration-dependent in endothelial cells.
“P‐II treatment significantly increased SIRT1 expression and reduced LOX‐1 expression”
- Also stated in: § Expression of LOX‐1, SIRT1 in control and hyperhomocysteinaemic mice · plain
“P‐II treatment markedly increased SIRT1 and decreased LOX‐1 expression compared to the HHcy group”
- Also stated in: § The LOX‐1 receptor and SIRT1 participate in P‐II ‐involved cell protection · plain
“Treatment with P‐II decreased concentration–dependently LOX‐1 expression in endothelial cells”
Quote in the paperSubstantial claim- Also stated in: § Expression of LOX‐1, SIRT1 in control and hyperhomocysteinaemic mice · plain
May combine two claims.
Findingown dataBlockade of SIRT1 or overexpression of LOX-1 attenuates the therapeutic effects of Picroside II.
“However, blockade of SIRT1 or overexpression of LOX‐1 attenuated the therapeutic effects of P‐II.”
- Also stated in: § DISCUSSION · plain
“overexpression of LOX‐1 attenuated P‐II protection”
- Also stated in: § DISCUSSION · plain
“blockade of SIRT1 with SIRT1 inhibitor, EX527, in vivo and SIRT1 siRNA in vitro, increased LOX‐1expression and attenuated P‐II protection”
Quote in the paperSubstantial claim- Also stated in: § DISCUSSION · plain
May combine two claims.
Findingown dataPlasma homocysteine was increased in animals fed with 1% methionine and reduced after treatment with Picroside II.
“Plasma Hcy was increased in animals fed with 1% methionine, while reduced after treatment with P‐II”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPlasma SOD activity was reduced in hyperhomocysteinemic mice and increased after Picroside II treatment.
“The plasma SOD activity was markedly reduced in the HHcy mice group but was increased significantly after treatment with P‐II”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPlasma MDA level was higher in hyperhomocysteinemic mice than in control mice, and Picroside II reversed the hyperhomocysteinemia-induced MDA increase.
“the level of plasma MDA in the HHcy mice was higher than that in the control group; however, treatment with P‐II reversed HHcy‐induced MDA increase”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataOverexpressing SIRT1 with SIRT1cDNA increases SIRT1 expression.
“overexpressing of SIRT1 with SIRT1cDNA increased SIRT1 (Figure 10C,D)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBlockade of SIRT1 increases LOX-1 expression, reactive oxygen species production, NF-κB activation, proinflammatory molecule expression, and cell apoptosis.
“blockade of SIRT1 with Ex527(in vivo) or siRNASIRT1(in vitro), LOX‐1 expression increased markedly, subsequently induced ROS production, NF‐κB activation, proinflammatory molecules expression and cell apoptosis”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataMice were randomly divided into five experimental groups.
“a total of 50 C57BL mice were randomly divided into five experimental groups”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductown dataThere was no significant difference in initial body weight, systolic blood pressure, or blood glucose among groups.
“There was no significant difference in initial body weight, systolic blood pressure, blood glucose among groups (all P > 0.05)”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenHUVECs were randomly divided into six groups.
“HUVECs were divided into six groups randomly”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenAssays were performed in triplicate and three independent experiments were performed.
“In this study, assays were performed in triplicate and three independent experiments were performed.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenExperiments were repeated in HUVECs from passage 2 to 7, with no differences observed between passages.
“Experiments were repeated in HUVECs from passage 2 to 7, with no differences observed between passages.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationThe exact mechanism by which hyperhomocysteinemia induces vascular endothelial injury remains unclear.
“but its exact mechanism remains unclear.4”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] Zhao J, Chen H, Liu N, et al. Role of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis. J Stroke Cerebrovasc Dis. 2017; 26: 2695‐ 2699. 28986198 source
The paper relies on this without support.
Whether Picroside II could inhibit hyperhomocysteinemia-induced endothelial injuries had not been studied.
“However, whether P‐II could inhibit HHcy‐induced endothelial injuries has not been studied.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Picroside II inhibits NF-κB activation in multiple inflammatory disease models, including endothelial injury and sepsis.
“Wang et al. [41] demonstrated that picroside II can inhibit NF-κB activation in hyperhomocysteinemia (HHcy)-induced endothelial injury.”
From Picroside II as a Potential Anti-Inflammatory Agent (2026) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Mouse methionine administration is described as diet and drinking water
MajorThe Animals methods say the HHcy model was established with a methionine-rich diet, whereas the Figure 2 caption says methionine was administered in drinking water.
“HHcy model was established by feeding C57BL mice with L‐methionine (w/w)‐rich diet for 12 weeks”
“the hyperhomocysteinaemic mice (HHcy) were treated with 2% (m·v‐1) methionine/drinking water for 3 months”
Five HUVEC groups are listed, not six
MinorThe listed groups comprise one control group, one Hcy group and three P‐II groups, totaling five rather than six.
Reported 6 · recomputed 5
“For experiments, HUVECs were divided into six groups randomly: a normal control group, a Hcy group, three P‐II groups.”
Figure 6 panel range conflicts with its ELISA panel labels
MinorThe caption identifies the figure as panels A-F but assigns the ELISA results to panels E, F and G; panel G falls outside the stated range.
“(A‐F). P‐II inhibits Hcy‐induced up‐regulation of inflammatory cytokines.”
“The mRNA levels and supernatant levels of IL‐6, IL‐8 and TNF‐α were determined separately by Real‐time PCR (A, B, C) and ELISA (E,F,G).”
Methionine concentration is stated as both 2% and 1%
MinorThe Figure 3 caption describes the hyperhomocysteinaemic mice as receiving 2% methionine in drinking water, then labels the treatment groups as 1% methionine groups.
“the hyperhomocysteinaemic mice (HHcy) were treated with 2% (m·v‐1) methionine/drinking water for 3 months”
“the 1% methionine group, the 1% methionine+P‐II group”
Cites
Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis
Homocysteine Studies Collaboration (2002) · JAMA · doi:10.1001/jama.288.16.2015 · Cited by 2,059 · see citing works
Ros and ros-mediated cellular signaling
Zhang, J., Wang, X., Vikash, V., Ye, Q., Wu, D., Liu, Y., & Dong, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/4350965 · Cited by 1,980 · cited 2× · see citing works
“common effector proteases activation, eventually leading to apoptosis.(24) In this study, we found that ROS generation in HUVECs”
BackgroundHofmann, M. A., Lalla, E., Lu, Y., Gleason, M. R., Wolf, B. M., Tanji, N., Ferran, L. J., Kohl, B., Rao, V., Kisiel, W., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10588 · Cited by 529 · see citing works
Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet
Mehta, J. L., Sanada, N., Hu, C. P., Chen, J., Dandapat, A., Sugawara, F., Satoh, H., Inoue, K., Kawase, Y., Jishage, K.-I., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.149724 · Cited by 444 · see citing works
Mehta, J. L., CHEN, J., Hermonat, P. L., Romeo, F., & Novelli, G. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.09.006 · Cited by 442 · see citing works
Li, D., & Mehta, J. L. (2000) · Circulation · doi:10.1161/01.cir.101.25.2889 · Cited by 421 · cited 1× · see citing works
“Much studies have shown that HHcy up‐regulated human mononuclear and endothelial cells LOX‐1 expression,(7,8) which prompts reactive oxygen species (ROS) formation,(8,9) induces pro‐apoptotic signal transduction and nitric oxide (NO) catabolism, consequently causing oxidative injury and the endothelial cells death.(10…”
BackgroundFree Radicals in Cross Talk Between Autophagy and Apoptosis
Kaminskyy, V. O., & Zhivotovsky, B. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5746 · Cited by 409 · cited 1× · see citing works
“Intracellular ROS levels are regulated by the balance between ROS formation and antioxidant enzymes.(23) In endothelial cells, NADPH oxidase is identified as a major source of oxidative stress.”
BackgroundKitada, M., Kume, S., Imaizumi, N., & Koya, D. (2011) · Diabetes · doi:10.2337/db10-0386 · Cited by 345 · see citing works
Zarzuelo, M. J., López-Sepúlveda, R., Sánchez, M., Romero, M., Gómez-Guzmán, M., Ungvary, Z., Pérez-Vizcaíno, F., Jiménez, R., & Duarte, J. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.02.015 · Cited by 202 · cited 1× · see citing works
“SIRT1, an important anti‐atherosclerosis molecule, protects the cardiovascular system from degeneration and oxidative injuries.(31,32) Previous reports have suggested that SIRT1 activation is an effective approach to manage HHcy‐induced oxidative stress,(33,34) and SIRT1 decreased the LOX‐1 expression level and NF‐κB…”
BackgroundRomero, M., Jiménez, R., Sánchez, M., López-Sepúlveda, R., Zarzuelo-Romero, M. J., O’Valle, F., Zarzuelo, A., Pérez‐Vizcaíno, F., & Duarte, J. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.03.007 · Cited by 139 · see citing works
Lu, J., Yang, J.-H., Burns, A. R., Chen, H.-H., Tang, D., Walterscheid, J. P., Suzuki, S., Yang, C.-Y., Sawamura, T., & Chen, C.-H. (2009) · Circulation Research · doi:10.1161/circresaha.108.190116 · Cited by 137 · cited 1× · see citing works
“Much studies have shown that HHcy up‐regulated human mononuclear and endothelial cells LOX‐1 expression,(7,8) which prompts reactive oxygen species (ROS) formation,(8,9) induces pro‐apoptotic signal transduction and nitric oxide (NO) catabolism, consequently causing oxidative injury and the endothelial cells death.(10…”
BackgroundSugimoto, K., Ishibashi, T., Sawamura, T., Inoue, N., Kamioka, M., Uekita, H., Ohkawara, H., Sakamoto, T., Sakamoto, N., Okamoto, Y., et al. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp177 · Cited by 124 · see citing works
Chen, X.-P., Xun, K.-L., Wu, Q., Zhang, T.-T., Shi, J.-S., & Du, G.-H. (2007) · Vascular Pharmacology · doi:10.1016/j.vph.2007.01.004 · Cited by 115 · see citing works
Wang, H. Q., Quan, T., He, T., Franke, T. F., Voorhees, J. J., & Fisher, G. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300574200 · Cited by 101 · cited 1× · see citing works
“By analysis of DNA fragmentation, apoptosis was examined using flow cytometry.(20) First, by using an Annexin V‐FITC apoptosis detection kit, HUVECs were washed and double‐stained.”
MethodAbais, J. M., Xia, M., Li, G., Gehr, T. W. B., Boini, K. M., & Li, P. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.009 · Cited by 89 · cited 1× · see citing works
“Emerging evidence suggests that HHcy accelerates atherosclerotic process as a result of increased oxidative stress.(22) Intracellular ROS levels are regulated by the balance between ROS formation and antioxidant enzymes.”
BackgroundRole of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis
Zhao, J., Chen, H., Liu, N., Chen, J., Gu, Y., Chen, J., & Yang, K. (2017) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2016.10.012 · Cited by 87 · cited 1× · see citing works
“Hyperhomocysteinemia (HHcy) can induces vascular endothelial injury, and has been determined to be one of the main risk factors for cardiovascular diseases,(2,3) but its exact mechanism remains unclear.(4) Lectin‐like oxLDL receptor‐1 (LOX‐1) is an essential receptor for oxide low‐density lipoprotein (oxLDL),(5) and p…”
BackgroundMa, C.-H., Chiua, Wu, C.-H., Jou, I.-M., Tu, Y.-K., Hung, C.-H., Hsieh, P.-L., & Tsai, K.-L. (2018) · Redox Biology · doi:10.1016/j.redox.2018.01.010 · Cited by 86 · see citing works
Apoptosis of Vascular Cells by Oxidized LDL
Kume, N., & Kita, T. (2004) · Circulation Research · doi:10.1161/01.res.0000119804.92239.97 · Cited by 85 · cited 1× · see citing works
“According to the caspase‐3 assay kit (Calbiochem) instructions, the activities of caspase‐3 were determined.(21) Briefly, we lysed and”
MethodHu, C.-P., Dandapat, A., Sun, L., Marwali, M. R., Inoue, N., Sugawara, F., Inoue, K., Kawase, Y., Jishage, K., Suzuki, H., et al. (2008) · Hypertension · doi:10.1161/hypertensionaha.108.115287 · Cited by 85 · see citing works
Chan, S.-H., Hung, C.-H., Shih, J.-Y., Chu, P.-M., Cheng, Y.-H., Lin, H.-C., Hsieh, P.-L., & Tsai, K.-L. (2018) · Redox Biology · doi:10.1016/j.redox.2017.08.016 · Cited by 76 · see citing works
Oxidized Low-Density Lipoprotein Receptor LOX-1 and Apoptosis in Human Atherosclerotic Lesions
Li, D. Y., Chen, H. J., Staples, E. D., Ozaki, K., Annex, B. H., Singh, B. K., Vermani, R., & Mehtat, J. L. (2002) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/107424840200700304 · Cited by 68 · see citing works
Hofmann, A., Brunssen, C., & Morawietz, H. (2018) · Vascular Pharmacology · doi:10.1016/j.vph.2017.10.002 · Cited by 68 · cited 1× · see citing works
“Lectin‐like oxLDL receptor‐1 (LOX‐1) is an essential receptor for oxide low‐density lipoprotein (oxLDL),(5) and plays a vital role in atherosclerotic process.(6) Much studies have shown that HHcy up‐regulated human mononuclear and endothelial cells LOX‐1 expression,(7,8) which prompts reactive oxygen species (ROS) for…”
BackgroundHuang, M., Zeng, S., Zou, Y., Shi, M., Qiu, Q., Xiao, Y., Chen, G., Yang, X., Liang, L., & Xu, H. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13657 · Cited by 66 · cited 3× · see citing works
“30 minutes.(17) Then, the lysate was centrifuged at 14 000 g for”
MethodInfluentialThree phenylethanoid glycosides and an iridoid glycoside from Picrorhiza scrophulariiflora
Li, J. X., Li, P., Tezuka, Y., Namba, T., & Kadota, S. (1998) · Phytochemistry · doi:10.1016/s0031-9422(98)00030-2 · Cited by 65 · cited 1× · see citing works
“The roots of this plant are of benefit, and as a traditional medicine, it is used for a number of conditions.(12,13) Picroside II (P‐II), one of the main active components of scrophularia extract, has shown its anti‐oxidative, anti‐inflammatory effects.”
BackgroundThampi, P., Stewart, B. W., Joseph, L., Melnyk, S. B., Hennings, L. J., & Nagarajan, S. (2007) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.09.014 · Cited by 52 · see citing works
WANG, L., LIU, X.-H., CHEN, H., CHEN, Z.-Y., WENG, X.-D., QIU, T., & LIU, L. (2015) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2015.2225 · Cited by 46 · see citing works
Holven, K. B., Scholz, H., Halvorsen, B., Aukrust, P., Ose, L., & Nenseter, M. S. (2003) · The Journal of Nutrition · doi:10.1093/jn/133.11.3588 · Cited by 42 · see citing works
Endothelial Dysfunction and Atherosclerosis: Focus on Novel Therapeutic Approaches
Briasoulis, Α., Tousoulis, D., Androulakis, E. S., et al. (2012) · Recent Advances in Cardiovascular Drug Discovery (Formerly Recent Patents on Cardiovascular Drug Discovery) · doi:10.2174/157489012799362386 · Cited by 42 · cited 1× · see citing works
“During the past decades, the convergence of clinical and basic evidence has demonstrated a fundamental role for endothelial dysfunction in pathogenesis and development of atherosclerotic diseases.(1) Homocysteine (Hcy) is derived from sulfur‐containing and non‐proteinogenic amino acid, and during the metabolism of met…”
BackgroundPicroside II Inhibits the MEK-ERK1/2-COX2 Signal Pathway to Prevent Cerebral Ischemic Injury in Rats
Wang, T., Zhai, L., Zhang, H., Zhao, L., & Guo, Y. (2015) · Journal of Molecular Neuroscience · doi:10.1007/s12031-015-0623-5 · Cited by 28 · see citing works
New secoiridoid Glycosides from the Roots of Picrorhiza Scrophulariiflora
Zou, L., Zhu, T.-F., Xiang, H., et al. (2008) · Molecules · doi:10.3390/molecules13092049 · Cited by 28 · cited 1× · see citing works
“The roots of this plant are of benefit, and as a traditional medicine, it is used for a number of conditions.(12,13) Picroside II (P‐II), one of the main active components of scrophularia extract, has shown its anti‐oxidative, anti‐inflammatory effects.”
BackgroundWang, Y. K., Hong, Y. J., Yao, Y. H., et al. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/503521 · Cited by 26 · see citing works
Self-citationHung, C.-H., Chan, S.-H., Chu, P.-M., & Tsai, K.-L. (2015) · Clinical Science · doi:10.1042/cs20150127 · Cited by 25 · cited 3× · see citing works
“Previous reports have suggested that SIRT1 activation is an effective approach to manage HHcy‐induced oxidative stress,(33,34) and SIRT1 decreased the LOX‐1 expression level and NF‐κB activation.(8,25) This statement is similar to our findings in the present study, as shown in”
BackgroundResultInfluentialChen, Y., Liu, H., Wang, X., Zhang, H., Liu, E., & Su, X. (2017) · Microvascular Research · doi:10.1016/j.mvr.2017.05.010 · Cited by 23 · see citing works
Self-citationLI, J.-Z., YU, S.-Y., MO, D., TANG, X.-N., & SHAO, Q.-R. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2014.2009 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Duan, H., Zhang, Q., Liu, J., Li, R., Wang, D., Peng, W., & Wu, C. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105599 · Cited by 257 · see citing works
Self-citationLi, T., Xu, L., Zheng, R., Wang, X., Li, L., Ji, H., & Hu, Q. (2019) · Phytomedicine · doi:10.1016/j.phymed.2019.153153 · Cited by 56 · see citing works
Xue, J., Zhang, Z., Sun, Y., Jin, D., Guo, L., Li, X., Zhao, D., Feng, X., Qi, W., & Zhu, H. (2023) · Journal of Inflammation Research · doi:10.2147/jir.s418166 · Cited by 52 · see citing works
“In hyperhomocysteinemia-induced HUVECs and mice models, picroside II may decrease EC injury in AS by inhibiting oxidative stress, inflammatory responses, and apoptosis through regulation of the SIRT1/LOX1 signaling pathway.(70) In LPS or Ox-LDL-induced cell models, active polypeptides from Hirudo may prevent AS onset…”
BackgroundZhou, Z.-Y., Shi, W., Zhang, J., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114137 · Cited by 33 · see citing works
Self-citationNatural Monoterpenes as Potential Therapeutic Agents against Atherosclerosis
Yang, J., Zhong, C., & Yu, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032429 · Cited by 34 · see citing works
“Picroside II HUVECs treated with homocysteine Protects against endothelial apoptosis induced by homocysteine Modulates SIRT1/LOX-1 pathway, and reduces cleaved Caspase-3 as well as Caspase-3 activity [76]”
BackgroundMethodInfluentialRole of hyperhomocysteinemia in atherosclerosis: from bench to bedside
Tian, W., Ju, J., Guan, B., Wang, T., Zhang, J., Song, L., & Xu, H. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2457527 · Cited by 31 · see citing works
“Recent research has demonstrated the protective effects of Picroside II (P-II) against HHcy-induced endothelial damage [162].”
Monoterpenes as Sirtuin-1 Activators: Therapeutic Potential in Aging and Related Diseases
Sousa, C., & Mendes, A. F. (2022) · Biomolecules · doi:10.3390/biom12070921 · Cited by 24 · see citing works
Chen, K., Chen, L., Ouyang, Y., Zhang, L., Li, X., Li, L., Si, J., Wang, L., & Ma, K. (2020) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2020.4497 · Cited by 19 · see citing works
“variety of cell types, including endothelial cells, mesangial cells and human umbilical vein endothelial cells (19-21).”
BackgroundLai, H., Liu, N., Zeng, L., Zhang, Y., & Pan, W. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.300460 · Cited by 17 · see citing works
“These results indicate that this signaling pathway may affect the spatial learning, memory, and cognitive functions of mice; this is similar to the findings of other studies (Liu et al., 2019; Wahl et al., 2019; Wang et al., 2019a; Zhong et al., 2019; Liang et al., 2020).”
BackgroundResultZhu, J., Liu, Y., He, X.-L., Kohlmeier, M., Zhou, L.-L., Shen, L., Yi, X.-X., Tang, Q., Cai, W., & Wang, B. (2020) · Annals of Nutrition and Metabolism · doi:10.1159/000507472 · Cited by 16 · see citing works
Partap, M., Chhimwal, J., Kumar, P., Kumar, D., Padwad, Y. S., & Warghat, A. R. (2022) · Process Biochemistry · doi:10.1016/j.procbio.2022.06.002 · Cited by 16 · see citing works
Zhang, L., Li, Z., Xing, C., Gao, N., & Xu, R. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.651582 · Cited by 14 · see citing works
“Studies have found that HHcy is mostly accompanied by an increase in reactive oxygen species (ROS) and inflammation (Hu et al., 2018; Yunkai et al., 2018), regardless of whether HHcy is a marker of abnormal metabolism in the body or an independent pathogenic factor for CVD. Additionally, the levels…”
BackgroundPiao, X., Sui, X., Liu, B., Cui, T., & Qi, Z. (2021) · BioMed Research International · doi:10.1155/2021/9945149 · Cited by 10 · see citing works
“Picroside II also had been reported to have inhibitory function on oxidative signaling pathway [11] and reduce inflammatory and apoptotic cells [33].”
BackgroundZheng, X., Li, W., Wang, M., Gao, H., Zhao, Y., Dong, P., & Han, H. (2025) · Medicinal Chemistry Research · doi:10.1007/s00044-025-03456-8 · Cited by 9 · see citing works
“Picroside II reversed LOX-1 overexpression, suppressed ROS generation, and reduced IL-6, IL-8, and TNF-α levels, demonstrating synergistic antioxidant, anti-in fl ammatory, and anti-apoptotic effects on vascular endothelium [107].”
Li, Y., Wang, L., Chen, Z., & Liu, X. (2019) · Acta Cirurgica Brasileira · doi:10.1590/s0102-865020190110000002 · Cited by 7 · see citing works
Kexin, J. I. A., Zhi, M. A., ZHANG, Y., Kaihong, X. I. E., Jianan, L. I., Jianzhi, W. U., Jiaorong, Q. U., Fanghong, L. I., & Xiaojiaoyang, L. I. (2024) · Chinese Journal of Natural Medicines · doi:10.1016/s1875-5364(24)60571-6 · Cited by 6 · see citing works
Li, H., Du, W., Yuan, Y., Xue, J., Li, Q., & Wang, L. (2021) · NeuroImmunoModulation · doi:10.1159/000519779 · Cited by 5 · see citing works
Gestational diabetes mellitus in the era of COVID-19: Challenges and opportunities
Xing, Y., Wang, H., Chao, C., Ding, X., & Li, G. (2024) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2024.102991 · Cited by 5 · see citing works
Wang, H., & Qian, J. (2025) · Cytotechnology · doi:10.1007/s10616-025-00783-x · Cited by 4 · see citing works
“Pic II has been reported as a natural antioxidant, and alleviates numerous diseases by inhibiting oxidative stress (Li et al. 2019; Wang et al. 2019b).”
Picroside II as a Potential Anti-Inflammatory Agent
Ren, Y., Liu, Z., Wei, L., Wang, Y., Wang, Y., Guo, Y., & Ma, Z. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18040499 · Cited by 2 · see citing works
“Wang et al. [41] demonstrated that picroside II can inhibit NF-κ B activation in hyperho-mocysteinemia (HHcy)-induced endothelial injury.”
Self-citationSun, Y., Ren, H., Han, X., et al. (2024) · Journal of the Pakistan Medical Association · doi:10.47391/jpma.10244 · Cited by 2 · see citing works
Jia, K., Ma, Z., Zhang, Y., Wu, J., Xue, X., Liu, R., Qu, J., Li, F., & Li, X. (2023) · doi:10.22541/au.168259699.91375234/v1
Picroside II alleviated non-alcoholic fatty liver disease via the AMPK-Nrf2 pathway.Preprint
Zhao, L., Chen, X., Li, Z., Wei, Y., Shen, B., Wang, Q., Cheng, J., & Feng, H. (2023) · Research Square · doi:10.21203/rs.3.rs-3692295/v1
Zhang, Y., Wang, X., Qiao, M., Liu, Y., Liu, T., Fu, S., Chu, Y., Wang, G., & Xj, M. (2026) · Biomedical Chromatography · doi:10.1002/bmc.70489
Wang, R., Zhang, W., Wang, F., Zhang, Y., & Li, J. (2026) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.71018
Yang, J., Song, W., Chen, K., Deng, J., Wang, A., Xu, P., Pan, H., Wang, K., Bian, Z., Chen, S., et al. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158811
- Authors
- Wang, Y., Hong, Y., Zhang, C., Shen, Y., Pan, Y. S., Chen, R. Z., Zhang, Q., & Chen, Y. H.
- Affiliations
- Tongji University (CN)
- Department of Radiology Fudan University Shanghai Cancer Center Shanghai China
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Wang, Yunkai
- Zhang, Qi
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2018-11-05
- Volume
- 23
- Issue
- 1
- Pages
- 464-475
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC6307770
- OpenAlex
- W2899905978
- Semantic Scholar
- 3c9040769200d8d2fd174aeded6b2fdd66fe8323
- Cited by
- 25
- References
- 34
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, other-oa)
- PubMed Central (submittedVersion, cc-by)
- Funders
- National Natural Science Foundation of China (8150021, 81102706)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- picroside II, hyperhomocysteinemia, endothelial injury, endothelial dysfunction, SIRT1, LOX-1, oxidative stress, inflammation, apoptosis, NF-κB, NADPH oxidase, reactive oxygen species, Scrophularia, human umbilical vein endothelial cells
- MeSH terms
- Animals, Antioxidants, Cell Line, Cinnamates, Endothelium, Humans, Inflammation, Mice, Inbred C57BL, Signal Transduction, Up-Regulation, NF-kappa B, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Hyperhomocysteinemia, Mice, Sirtuin 1, Iridoid Glucosides, Human Umbilical Vein Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
